A new targeted alpha therapy is showing promise for patients whose thyroid cancer no longer responds to radioactive iodine, the standard beta-emitting treatment. In a first-in-human study, investigators found that a single dose of the alpha-emitting radionuclide\u00a0211At (astatine) was both well-tolerated and effective, achieving disease control without molecularly targeted drugs. The findings were published in the December issue of\u00a0The Journal of Nuclear Medicine.<\/p>\n
Beta-emitting radioactive iodine is the standard treatment for patients with recurrent or metastatic differentiated thyroid cancer (DTC) after total thyroidectomy. However, despite repeated administration, some patients experience disease progression and are classified as refractory to radioactive iodine. At that point, molecular-targeted agents, such as kinase inhibitors, are used to treat radioactive iodine-resistant DTC.<\/p>\n
Molecular-targeted agents can be challenging for patients to take, as they require daily oral administration and are associated with a high rate of adverse effects, including proteinuria and dermatologic toxicity. Therefore, there is a clinical need for next-generation radiopharmaceutical therapy with improved tolerability and efficacy that can be used to treat radioactive iodine-refractory patients.”<\/p>\n
Tadashi Watabe, MD, PhD, FANMB, nuclear medicine physician, Graduate School of Medicine, University of Osaka, Japan<\/p>\n
To address this issue, Watabe and colleagues developed a targeted alpha-therapy using the radionuclide\u00a0211At-NaAt. In a phase I clinical trial, they utilized a dose escalation model (1.25, 2.5, and 3.5 MBq\/kg) to assess the adverse events, pharmacokinetics, absorbed dose, and therapeutic efficacy of<\/a> a single intravenous dose of\u00a0211At-NaAt in patients with radioactive iodine-refractory DTC. Response was evaluated by thyroglobulin measurement, CT imaging, and\u00a0131I SPECT imaging.<\/p>\n The researchers found that targeted alpha-therapy using\u00a0211At-NaAt can be safely administered to patients with DTC. Although dose-limiting toxicities were observed with the 3.5 MBq\/kg dose, toxicities remained within a tolerable range. Preliminary evidence of efficacy was observed in some patients treated with either 2.5 or 3.5 MBq\/kg, including thyroglobulin reductions of greater than 50 percent and decreased uptake in radioactive iodine-avid lesions on\u00a0131I SPECT.<\/p>\n “Our findings provide the first evidence that\u00a0211At based therapy is both feasible and therapeutically promising in patients who no longer respond to conventional radioactive iodine,” stated Watabe. “Because\u00a0211At (astatine) therapy may achieve disease control without requiring molecular targeted drugs, it has the potential to reduce treatment burden, limit adverse effects associated with systemic therapies, and broaden access to effective care for patients with refractory disease.”<\/p>\n “In addition,” he noted, “211At can be produced using accelerator cyclotrons, and its availability will expand globally as more production facilities come online. The successful clinical application of\u00a0211At in this study marks an important milestone for the field, opening the door to widespread adoption of cyclotron-based alpha-therapy and accelerating future innovations in molecular imaging and targeted radionuclide therapy.”<\/p>\n Source:<\/p>\n Society of Nuclear Medicine and Molecular Imaging<\/a><\/p>\n Journal reference:<\/p>\n